Summary The typical older adult experiences declines in brain structure and cognitive function, but these mean declines occur in the context of what can be very different individual trajectories. The purpose of this project is to measure individual differences and changes in self-regulation (control of thoughts, emotions, behaviors, and impulses) over time in older adults, and to link self-regulation to physical activity, inflammation, and trajectories of neurocognitive health. This is a competing renewal of this longitudinal study, which began in 2001 and received R01 funding in 2006, submitted by a research team with expertise in aging, self-regulation, exercise science, neuropsychology, neuroimaging, and longitudinal design and analysis. The previous renewal period focused on relationships among facets of self-regulation and their relationship to immunological and cardiovascular health. The renewal continues assessment of these measures to provide continuity in this longitudinal dataset and adds innovation in the inclusion of repeated neuroimaging and assessment of infectious disease burden. Specifically, the aims of the study are: (1) to test the effects of facets of self- regulation (conscientiousness, self-regulation, executive cognitive function, and heart rate variability) on measures of neurocognitive health associated with aging and risk for neurological disease; (2) to test the degree to which the relationship between self-regulation and neurocognitive health is mediated by physical activity and inflammation; (3) to test whether neurocognitive health associated with executive cognitive functions (e.g., dorsolateral frontal lobe volume) contributes to better self-regulation, higher physical activity, and lower inflammation; and (4) to test effects of infectious disease burden (latent viruses, Toxoplasma gondii) on self-regulation, inflammation, and neurocognitive health. At 6-month intervals, older adults (N = 175) will complete measures of self-reported self-regulation; executive cognitive functions including inhibition, shifting, and working memory; and resting HRV. Physical activity, BMI, and waist circumference will be measured at each visit. Blood draws will be synchronized with these visits, and assays performed on these samples will capture serum proinflammatory cytokines and antibodies against latent infections. The sample has follow-back data on many of these measures from 1-15 years, and an eligible subset (N = 90) will already have baseline neuroimaging. Neuroimaging will be repeated twice at 2-year intervals. This renewal will be innovative in its longitudinal assessment of a dynamic system that includes brain, behavior, and immunity; integration of neuroimaging measures with other domains of healthy and unhealthy aging; and multimodal assessment of neurocognitive health, including subjective cognitive health, cognitive function, volumetric imaging measures, connectivity, fractional anisotropy, and resting cerebral blood flow.